Towards complete sets of farnesylated and geranylgeranylated proteins.
Three different prenyltransferases attach isoprenyl anchors to C-terminal motifs in substrate proteins. These lipid anchors serve for membrane attachment or protein-protein interactions in many pathways. Although well-tolerated selective prenyltransferase inhibitors are clinically available, their m...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2007-04-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC1847700?pdf=render |
| _version_ | 1819150287095463936 |
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| author | Sebastian Maurer-Stroh Manfred Koranda Wolfgang Benetka Georg Schneider Fernanda L Sirota Frank Eisenhaber |
| author_facet | Sebastian Maurer-Stroh Manfred Koranda Wolfgang Benetka Georg Schneider Fernanda L Sirota Frank Eisenhaber |
| author_sort | Sebastian Maurer-Stroh |
| collection | DOAJ |
| description | Three different prenyltransferases attach isoprenyl anchors to C-terminal motifs in substrate proteins. These lipid anchors serve for membrane attachment or protein-protein interactions in many pathways. Although well-tolerated selective prenyltransferase inhibitors are clinically available, their mode of action remains unclear since the known substrate sets of the various prenyltransferases are incomplete. The Prenylation Prediction Suite (PrePS) has been applied for large-scale predictions of prenylated proteins. To prioritize targets for experimental verification, we rank the predictions by their functional importance estimated by evolutionary conservation of the prenylation motifs within protein families. The ranked lists of predictions are accessible as PRENbase (http://mendel.imp.univie.ac.at/sat/PrePS/PRENbase) and can be queried for verification status, type of modifying enzymes (anchor type), and taxonomic distribution. Our results highlight a large group of plant metal-binding chaperones as well as several newly predicted proteins involved in ubiquitin-mediated protein degradation, enriching the known functional repertoire of prenylated proteins. Furthermore, we identify two possibly prenylated proteins in Mimivirus. The section HumanPRENbase provides complete lists of predicted prenylated human proteins-for example, the list of farnesyltransferase targets that cannot become substrates of geranylgeranyltransferase 1 and, therefore, are especially affected by farnesyltransferase inhibitors (FTIs) used in cancer and anti-parasite therapy. We report direct experimental evidence verifying the prediction of the human proteins Prickle1, Prickle2, the BRO1 domain-containing FLJ32421 (termed BROFTI), and Rab28 (short isoform) as exclusive farnesyltransferase targets. We introduce PRENbase, a database of large-scale predictions of protein prenylation substrates ranked by evolutionary conservation of the motif. Experimental evidence is presented for the selective farnesylation of targets with an evolutionary conserved modification site. |
| first_indexed | 2024-12-22T14:15:06Z |
| format | Article |
| id | doaj.art-4577f5c67d9a40e1bbc30971d1063474 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-22T14:15:06Z |
| publishDate | 2007-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-4577f5c67d9a40e1bbc30971d10634742022-12-21T18:23:08ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582007-04-0134e6610.1371/journal.pcbi.0030066Towards complete sets of farnesylated and geranylgeranylated proteins.Sebastian Maurer-StrohManfred KorandaWolfgang BenetkaGeorg SchneiderFernanda L SirotaFrank EisenhaberThree different prenyltransferases attach isoprenyl anchors to C-terminal motifs in substrate proteins. These lipid anchors serve for membrane attachment or protein-protein interactions in many pathways. Although well-tolerated selective prenyltransferase inhibitors are clinically available, their mode of action remains unclear since the known substrate sets of the various prenyltransferases are incomplete. The Prenylation Prediction Suite (PrePS) has been applied for large-scale predictions of prenylated proteins. To prioritize targets for experimental verification, we rank the predictions by their functional importance estimated by evolutionary conservation of the prenylation motifs within protein families. The ranked lists of predictions are accessible as PRENbase (http://mendel.imp.univie.ac.at/sat/PrePS/PRENbase) and can be queried for verification status, type of modifying enzymes (anchor type), and taxonomic distribution. Our results highlight a large group of plant metal-binding chaperones as well as several newly predicted proteins involved in ubiquitin-mediated protein degradation, enriching the known functional repertoire of prenylated proteins. Furthermore, we identify two possibly prenylated proteins in Mimivirus. The section HumanPRENbase provides complete lists of predicted prenylated human proteins-for example, the list of farnesyltransferase targets that cannot become substrates of geranylgeranyltransferase 1 and, therefore, are especially affected by farnesyltransferase inhibitors (FTIs) used in cancer and anti-parasite therapy. We report direct experimental evidence verifying the prediction of the human proteins Prickle1, Prickle2, the BRO1 domain-containing FLJ32421 (termed BROFTI), and Rab28 (short isoform) as exclusive farnesyltransferase targets. We introduce PRENbase, a database of large-scale predictions of protein prenylation substrates ranked by evolutionary conservation of the motif. Experimental evidence is presented for the selective farnesylation of targets with an evolutionary conserved modification site.http://europepmc.org/articles/PMC1847700?pdf=render |
| spellingShingle | Sebastian Maurer-Stroh Manfred Koranda Wolfgang Benetka Georg Schneider Fernanda L Sirota Frank Eisenhaber Towards complete sets of farnesylated and geranylgeranylated proteins. PLoS Computational Biology |
| title | Towards complete sets of farnesylated and geranylgeranylated proteins. |
| title_full | Towards complete sets of farnesylated and geranylgeranylated proteins. |
| title_fullStr | Towards complete sets of farnesylated and geranylgeranylated proteins. |
| title_full_unstemmed | Towards complete sets of farnesylated and geranylgeranylated proteins. |
| title_short | Towards complete sets of farnesylated and geranylgeranylated proteins. |
| title_sort | towards complete sets of farnesylated and geranylgeranylated proteins |
| url | http://europepmc.org/articles/PMC1847700?pdf=render |
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